In recent years, mRNA technology has demonstrated broad application prospects in vaccine development, protein replacement therapy, and tumor immunotherapy, owing to its flexible sequence design and high expression efficiency. However, overcoming the limitations ofin vivodelivery to achieve effective transport of mRNA drugs to target tissues and cells remains a major challenge for further development. Lipid nanoparticles (LNPs) are currently one of the most widely used mRNA delivery vehicles. Nevertheless, conventional LNP systems still exhibit significant tissue-biased distributionin vivo, particularly facing challenges in delivery efficiency and specificity to extrahepatic tissues such as the lungs. Therefore, developing mRNA delivery systems with tissue-targeting capabilities has become an important research direction in the nucleic acid therapeutics field. Recently, a research team from Peking University published a study inActa Pharmaceutica Sinica B, proposing a Synergistic Targeted Lipid Nanoparticle (SynTar LNP) platform. This platform combines lipid composition optimization with antibody-mediated targeted modification to enhance mRNA delivery efficiency to the lungs, providing a novel technical approach for the treatment of pulmonary diseases and tumor immunotherapy. From Lipid Composition Optimization to Antibody Functionalization: Constructing the SynTar Delivery Platform To improve mRNA delivery to the lungs, the research team first optimized conventional LNP composition based on the selective organ targeting (SORT) strategy through lipid substitution. Using the SM-102 LNP system as the foundation, they replaced DSPC with DOTAP and DMG-PEG with DSPE-PEG-Mal, constructing a four-component lung-targeting LNP system (4C-DOTAP LNP) composed of SM-102, cholesterol, DOTAP, and DSPE-PEG-Mal. The study found that 4C-DOTAP LNP containing 30% DOTAP exhibited superior pulmonary delivery capacity compared to the conventional five-component DOTAP LNP system, with approximately a 2-fold increase in lung fluorescence signal, while maintaining a particle size of around 100 nm and a low polydispersity index (PDI < 0.2), demonstrating good stability. On this basis, the research team utilized the terminal maleimide group of DSPE-PEG-Mal to conjugate anti-CD31 antibodies via thiol-maleimide reaction, providing a linkage foundation for LNP functionalization. Further comparison revealed that Anti LNP constructed with DSPE-PEG-Mal achieved approximately 5.4-fold higher lung-targeting efficiency than the DMG-PEG-Mal system, while reducing non-target tissue expression in the liver and spleen. This may be attributed to the longer C18 hydrophobic chain of DSPE compared to the C14 chain of DMG-PEG-Mal, which enables more stable integration into the LNP lipid layer and helps maintain delivery efficacy after antibody modification. Based on these advantages, the research team further applied anti-CD31 antibody modification to 4C-DOTAP LNP to construct the SynTar ...

In the biopharmaceutical field, PEGylation technology continues to attract significant industry attention as a key means of improving drug performance. Sinopeg has deep expertise in the PEG derivative sector and is committed to providing pharmaceutical companies and research institutions with products and technical support covering a wide range of application scenarios. Diverse Product Lines Sinopeg offers a broad variety of PEG derivatives in terms of structural types, with a product matrix encompassing both linear and specialized structures: Linear PEG Derivatives:Including mono-functionalized, di-functionalized, and hetero-bifunctionalized types, catering to different coupling directions and connection modes. These are suitable for classic applications such as protein modification and surface functionalization. Specialized Structure PEG Derivatives:Featuring multi-arm (2-arm, 3-arm, 4-arm, 6-arm, 8-arm), V-shaped, Y-shaped, and other topological structures, providing structural support for cutting-edge scenarios including hydrogel construction, targeted delivery, and multivalent conjugation. Sinopeg also has the capability to produce monodisperse PEG derivatives, offering a series of products ranging from low to high molecular weights. This diverse combination of structures and specifications facilitates flexible selection based on customer requirements. Rich Functional Group Offerings The application value of PEG derivatives depends significantly on the types of functional groups at their terminal ends—these groups act as "molecular handles" that enable selective conjugation with specific groups on drug molecules, proteins, antibodies, or nanoparticle surfaces. Sinopeg provides a comprehensive selection of functional groups covering mainstream conjugation chemistries: Classic Conjugation Functional Groups:Including amino (-NH₂), carboxyl (-COOH), aldehyde (-CHO), thiol (-SH), acrylate (AA), methacrylate (MA), etc., covering a variety of classic conjugation strategies and material preparation needs. Amino-Reactive Functional Groups:Including succinimidyl esters (e.g., SC, SCM, SS, SVA), nitrophenyl carbonate (NPC), etc., which efficiently couple with primary amino groups under mild conditions and are commonly used tools for protein, peptide, and antibody modification. Thiol-Reactive Functional Groups:Such as maleimide (MAL) and vinyl sulfone (VS), which selectively conjugate with thiol-containing biomolecules and are suitable for modification scenarios such as antibody-drug conjugates (ADCs). Click Chemistry Functional Groups:Such as azide (N₃) and alkyne (Alkyne), enabling efficient, highly selective bioorthogonal conjugation under mild conditions via click chemistry, widely applied in mRNA delivery, nanomaterial modification, and other fields. More importantly, within the same product line, different functional group versions can be matched with corresponding PEG structures (linear, multi-arm, Y-shaped, etc.), forming a "structure × function...

In Vivo Gene Editing Therapies Offer Root-Cause Treatment for Genetic Diseases, but Efficient and Precise Liver-Targeted Delivery Remains a Critical Hurdle for Clinical Translation. Lipid Nanoparticles (LNPs), as the Mainstream Non-Viral Vector, Have Made Functionalization a Core Strategy for Enhancing Targeting Efficiency. Xiamen Sinopeg Biotech Co., Ltd. (Sinopeg) is proud to introduce its independently innovated structure,GalNAc-PEG-DTA-5-2K. This liver-targeting functional PEG lipid, specifically designed for LNP systems, aims to provide gene editing and siRNA drug developers with a high-performance excipient option featuring a clear IP profile. It is set to empower the advancement of liver-targeted therapeutic pipelines. I. Delivery Challenges for Liver-Targeted Gene Editing The in vivo application of gene editing therapies hinges on the safe and precise delivery of the CRISPR system (editor mRNA and guide RNA) to target cells. LNPs have become a recognized in vivo delivery platform, owing to their excellent encapsulation and protection capabilities, low immunogenicity, and scalability for manufacturing. However, after intravenous administration, conventional LNPs are largely cleared by liver immune cells or degraded in circulation, with a limited fraction reaching hepatocytes. This restricts therapeutic efficacy and may increase off-target risks. Thus, endowing LNPs with active liver-targeting capabilities is an inevitable direction for technological advancement. Among targeting strategies, the N-acetylgalactosamine (GalNAc) ligand stands out as a well-established and extensively validated liver-targeting approach. Its receptor, the asialoglycoprotein receptor (ASGPR), is highly expressed on the surface of hepatocytes and is not found at significant levels in other tissues. This makes the GalNAc-ASGPR pathway a highly efficient and specific natural targeting mechanism. GalNAc ligands can specifically bind to ASGPR, facilitating efficient cellular uptake via receptor-mediated endocytosis. Integrating this strategy into LNP systems offers a new design dimension for the hepatic delivery of gene editing drugs. II. Industry Trend: GalNAc-PEG Lipids Emerge as a Consensus Direction for Liver-Targeted LNPs In the field ofin vivogene editing, cutting-edge research from both international and domestic fronts is converging on the GalNAc-PEG lipid technology pathway. U.S.-based Verve Therapeutics, in its second-generationin vivobase editing therapy, has incorporated GalNAc targeting ligands into its LNP delivery system, modifying the LNP surface with GalNAc-containing PEG lipids. This upgrade aims to enhance liver targeting, increase drug concentration within hepatocytes, thereby achieving effective editing at lower doses and improving drug tolerability and safety. Drawing on clinical experience from its first-generation product, Verve has made a clear targeted enhancement to its delivery vehicle, reflecting that GalNAc-LNPs have become a technological...